Antibody-dependent cellular cytotoxicity and neutralization of human immunodeficiency virus type 1 by high affinity cross-linking of gp41 to human macrophage Fc IgG receptor using bispecific antibody

1 Laboratoire de Neuropathologie expérimentale et Neurovirologie, CRSSA, DSV/DPTE, Commissariat à l'Energie Atomique, BP 6, 92265 Fontenay-aux-Roses Cedex 2 Immuno-Designed-Molecules, 128 Boulevard Richard Lenoir, 75011 Paris and 3 CNTS, BP100, 91943 Les Ulis, France Human monocytes/macrophages, which express Fc receptors for IgG are involved in human immuno-deficiency virus type 1 (HIV-1) infection and pathogenesis. These receptors are known to mediate numerous immunological functions including cell-mediated killing and possibly targeting of HIV to the lysophagosome monocyte-derived macrophage (MDM) entry route for virus neutralization. To study both activities in HIV-1 infection, MDM Fc RI was specifically selected using bispecific antibody (Bs-Ab) containing whole human monoclonal antibody against gp41 and the Fab' fragment of murine anti-Fc RI 22·2 antibody. Bs-Ab was found to mediate potent antibody-dependent cellular cytotoxicity and virus neutralization. Received 9 August 1993; accepted 13 December 1993.